Genetic Variant DTWD2:p.Asp53Val (chr5-118988354-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_173666.4(DTWD2):c.158A>T(p.Asp53Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,410,320 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D53G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DTWD2
NM_173666.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.979

Publications

0 publications found

Variant links:

Genes affected

DTWD2 (HGNC:19334): (DTW domain containing 2) Enables tRNA-uridine aminocarboxypropyltransferase activity. Involved in tRNA modification. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DTWD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTWD2	NM_173666.4 link	c.158A>T	p.Asp53Val	missense_variant	Exon 1 of 6	ENST00000510708.6	NP_775937.1	Q8NBA8-1
DTWD2	XM_011543338.4 link	c.158A>T	p.Asp53Val	missense_variant	Exon 1 of 7		XP_011541640.3
DTWD2	NM_001308081.2 link	c.-205A>T		upstream_gene_variant			NP_001295010.1	Q8NBA8-2
DTWD2	XM_011543340.3 link	c.-205A>T		upstream_gene_variant			XP_011541642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DTWD2	ENST00000510708.6 link	c.158A>T	p.Asp53Val	missense_variant	Exon 1 of 6	1	NM_173666.4	ENSP00000425048.1	Q8NBA8-1
DTWD2	ENST00000515439.7 link	c.158A>T	p.Asp53Val	missense_variant	Exon 1 of 4	5		ENSP00000424221.2	D6RBD8
DTWD2	ENST00000506980.2 link	n.158A>T		non_coding_transcript_exon_variant	Exon 1 of 5	5		ENSP00000425016.1	D6REE2
DTWD2	ENST00000304058.8 link	c.-205A>T		upstream_gene_variant		1		ENSP00000302892.4	Q8NBA8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

160256

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1410320

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

697678

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31402

American (AMR)

AF:

0.00

AC:

AN:

37490

Ashkenazi Jewish (ASJ)

AF:

0.0000398

AC:

AN:

25156

East Asian (EAS)

AF:

0.00

AC:

AN:

36474

South Asian (SAS)

AF:

0.00

AC:

AN:

81020

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4254

European-Non Finnish (NFE)

AF:

9.19e-7

AC:

AN:

1088572

Other (OTH)

AF:

0.00

AC:

AN:

58334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;T

Eigen

Benign

0.016

Eigen_PC

Benign

-0.032

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.76

T;T

M_CAP

Pathogenic

0.31

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.97

L;.

PhyloP100

0.98

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.12

Sift

Benign

0.14

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.84

P;.

Vest4

0.52

MutPred

0.14

Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);

MVP

0.34

MPC

0.16

ClinPred

0.89

GERP RS

4.2

PromoterAI

-0.047

Neutral

(source)

Varity_R

0.30

gMVP

0.38

Mutation Taster

=74/26

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over